Rab-3 is a member of a family of small GTP binding proteins which have been implicated in the trafficking of synaptic vesicles. Rab family members and the structurally related to p2lras product of the ras oncogene cycle between GTP- and GDP-bound forms. Each Rab protein appears act in a specific form of vesicle transport. This specificity, together with the regulatory potential of their cycling mechanism suggests a role for RAB proteins in the regulation of trafficking. The actual role which Rab proteins play in the transport and membrane fusion remains a unclear, however. This proposal addresses the role of Rab3 in synaptic vesicle transport and fusion. The experiments presented use C. elegans as a genetic and molecular system for the analysis of Rab3 function. Genetic and molecular methods will first be used to isolate new rab-3 alleles, and then to analyze the Rab3 functional pathway through of enhancer and suppressor analyses. These studies should yield novel information about Rab-3 function and synaptic vesicle transport in general. The results from these experiments will aid in the dissection of the general function of the Rab proteins and the factors modulate their function.